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4 results on '"Médecine légale, Anatomo-pathologie et Paléopathologie [CHU Raymond Poincaré]"'

1. Pannexin-1 channel opening is critical for COVID-19 pathogenesis

Author

Geoffroy Lorin de la Grandmaison, Antonio Cibelli, David C. Spray, Juan E. Tichauer, Jean Dubuisson, Arielle Rosenberg, Ross H. Luu, Sandrine Belouzard, Eliana Scemes, Elisabeth Cramer-Bordé, Morgane Bomsel, Djillali Annane, Maximiliano Rovegno, Andrea Cottignies-Calamarte, Silvana Valdebenito, Eliseo A. Eugenin, Calude Capron, [Institut Cochin] Departement Infection, immunité, inflammation, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), The University of Texas Medical Branch (UTMB), New York Medical College (NYMC), Albert Einstein College of Medicine [New York], Pontificia Universidad Católica de Chile (UC), Service de Virologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Ambroise Paré [AP-HP], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies Infectieuses et Tropicales [CHU Raymond Poincaré], Hôpital Raymond Poincaré [AP-HP], Service médical des soins intensifs [CHU Raymond Poincaré], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Médecine légale, Anatomo-pathologie et Paléopathologie [CHU Raymond Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The authors acknowledge financial support from the National Institutes of Health grant: MH096625/MH128082, The National Institute of Neurological Disorders and Stroke, NS105584, and UTMB internal funding (to E.A.E).Also, funding from the Flash COVID fund from both ANR and Fondation pour la Recherche Medicale (ANR-20-COVI-000 and AO2020- MUCOLUNG-ANR Flash COVID-19 - FRM) was provided to M.B., ANR-20-COVI-0024,MUCOLUNG,Rôle des cellules pulmonaires infectées par le SRAS-CoV-2 et réponse humoral dans l' évolution du COVID-19: de la physiopathologie au test de médicaments candidats dans les modèles de cellules muqueuses(2020), Bomsel, Morgane, and Rôle des cellules pulmonaires infectées par le SRAS-CoV-2 et réponse humoral dans l' évolution du COVID-19: de la physiopathologie au test de médicaments candidats dans les modèles de cellules muqueuses - - MUCOLUNG2020 - ANR-20-COVI-0024 - COVID-19 - VALID

Subjects
Cell biology, Human coronavirus 229E, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, viruses, Connexin, Endocytosis, medicine.disease_cause, Article, lung, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Multiplicity of infection, Virology, medicine, purinergic, education, Furin, Molecular physiology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Coronavirus, 0303 health sciences, education.field_of_study, Multidisciplinary, biology, Chemistry, COVID-19, virus diseases, Pannexin, biology.organism_classification, respiratory tract diseases, 3. Good health, ATP, Allograft inflammatory factor 1, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030217 neurology & neurosurgery
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly rampaged worldwide, causing a pandemic of coronavirus disease (COVID -19), but the biology of SARS-CoV-2 remains under investigation. We demonstrate that both SARS-CoV-2 spike protein and human coronavirus 229E (hCoV-229E) or its purified S protein, one of the main viruses responsible for the common cold, induce the transient opening of Pannexin-1 (Panx-1) channels in human lung epithelial cells. However, the Panx-1 channel opening induced by SARS-CoV-2 is greater and more prolonged than hCoV-229E/S protein, resulting in an enhanced ATP, PGE2, and IL-1β release. Analysis of lung lavages and tissues indicate that Panx-1 mRNA expression is associated with increased ATP, PGE2, and IL-1β levels. Panx-1 channel opening induced by SARS-CoV-2 spike protein is angiotensin-converting enzyme 2 (ACE-2), endocytosis, and furin dependent. Overall, we demonstrated that Panx-1 channel is a critical contributor to SARS-CoV-2 infection and should be considered as an alternative therapy., Graphical abstract, Cell biology; Molecular physiology; Virology

Published
2021
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2. Postmortem fatal and non-fatal concentrations of amlodipine

Author

C. Mayer-Duverneuil, Jean-Claude Alvarez, A. Knapp-Gisclon, G. Lorin de la Grandamison, J. Cappy, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [AP-HP], Médecine légale, Anatomo-pathologie et Paléopathologie [CHU Raymond Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], and CCSD, Accord Elsevier

Subjects
Male, medicine.medical_specialty, Population, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Autopsy, 01 natural sciences, Mass Spectrometry, Pathology and Forensic Medicine, Forensic Toxicology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Post-mortem redistribution, 030216 legal & forensic medicine, Amlodipine, education, Aged, Whole blood, education.field_of_study, business.industry, 010401 analytical chemistry, Calcium Channel Blockers, Coronary heart disease, [SHS.ANTHRO-BIO] Humanities and Social Sciences/Biological anthropology, 3. Good health, 0104 chemical sciences, Blood pressure, Quartile, Post-mortem concentrations, Postmortem Changes, Cardiology, Female, business, Law, Dihydropyridine Calcium Channel Blocker, Chromatography, Liquid, medicine.drug
Abstract

International audience; Amlodipine is a dihydropyridine calcium channel blocker widely used in the treatment of high blood pressure and coronary heart disease. Intoxication can lead to reflex tachycardia following massive hypotension and death. The objective of this work was to study the post-mortem concentrations of amlodipine in 62 patients in order to determine whether the use of the reference concentrations from the living patients was applicable in postmortem setting, and to define more precisely the fatal and non-fatal postmortem concentrations of amlodipine. The amlodipine concentrations were measured in femoral whole blood by LC–MS/MS validated method. When sufficient information was available, the data were classified into 2 different groups, based on the conclusions of the autopsy and toxicological results: G1: non-toxic death and G2: fatal poisoning involving amlodipine alone or as part of a multidrug poisoning. The median concentration of amlodipine [1st quartile - 3rd quartile] of the whole population (n = 62) was 81 [42–134] ng/mL. Twenty-two cases were classified as G1 and thirteen as G2. The observed median [1st quartile - 3rd quartile] concentration of amlodipine was 66 [40.5–79.5] ng/mL in G1 and 240 [170–404] ng/mL in G2. The median concentrations observed in “non-toxic” deaths (66 ng/mL) were three times higher than those usually observed in living patients. Amlodipine distribution ratio between plasma and whole blood concentrations seems insufficient to explain this difference and postmortem redistribution from organs should be considered, and could suggest the same redistribution pattern for other drugs belonging to the same family.

Published
2020
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3. Fatal intoxication with ivabradine: First case report

Author

G. Lorin de la Grandamison, C. Mayer-Duverneuil, Jean-Claude Alvarez, C. Rambaud, M. Zerah, A. Knapp-Gisclon, Merlan, Justine, Hôpital Raymond Poincaré [AP-HP], Médecine légale, Anatomo-pathologie et Paléopathologie [CHU Raymond Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Infection et inflammation (2I), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Bradycardia, [SDV]Life Sciences [q-bio], Ethyl acetate, Poison control, Blood concentration, 01 natural sciences, Pathology and Forensic Medicine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Ivabradine, 030216 legal & forensic medicine, Whole blood, Zopiclone, business.industry, 010401 analytical chemistry, medicine.disease, 0104 chemical sciences, [SDV] Life Sciences [q-bio], Blood pressure, chemistry, Anesthesia, Heart failure, medicine.symptom, business, Law, Fatal intoxication, Viscera concentrations, medicine.drug
Abstract

International audience; Ivabradine is a bradycardic drug used worldwide in the treatment of chronic stable angina and chronic heart failure. We presented here a case of a 61-year-old woman who was admitted to emergency department for overdose. She presented with drowsiness, bradycardia (45bpm) and a low blood pressure (116/21mmHg). She died ten hours after admission from multiple organ failure. Ivabradine was quantified in different matrices sampled during autopsy using a method on LC-MS/MS (TSQ Vantage Thermo Fisher Scientific®), after a double liquid-liquid extraction with a mixture of hexane/ethyl acetate (1/1; v/v) and then chloroform/isopropanol (80/20; v/v). Chromatographic separation was achieved using a Hypersyl gold PFP column (200×2.1mm, 1.9μm) and an acetonitrile/formiate 2mM, 0.1% formic acid buffer gradient. Method was fully validated on whole blood. The mean overall recovery was 90%. Linearity was validated in the 5-500ng/mL range, with intra and inter-day precision lower than 14.3%. The ivabradine concentration found in patient post-mortem blood was 1210ng/mL. Ivabradine was also quantified in different viscera like lung (2910ng/g), kidney (1510ng/g), liver (1050ng/g), heart (900ng/g), and brain (110ng/g). The vitreous humor concentration was 760ng/mL. Pregabalin and zopiclone were also found in blood at 50μg/mL and 206ng/mL, respectively. This case seems to be the first report of a fatal intoxication involving ivabradine and the first published concentrations in organs.

Published
2020
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4. Which placebo to cure depression? A thought-provoking network meta-analysis

Author

Bruno Falissard, Florian Naudet, Jean Michel Reymann, Philippe Charlier, Bruno Millet, Anne Solène Maria, Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Service de Psychiatrie, Centre Hospitalier Guillaume Régnier, Troubles du comportement alimentaire de l'adolescent (UMR_S 669), Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Médecine légale, Anatomo-pathologie et Paléopathologie [CHU Raymond Poincaré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Laboratoire Ethique Politique et Santé (EA 4569), Université Paris Descartes - Paris 5 (UPD5), Unité de Méthodologie des Essais Thérapeutiques, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire de Pharmacologie Expérimentale et Clinique, Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR)-Université de Rennes (UR)-Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), Service de Santé Publique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, This paper was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM)., Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Laboratoire de Pharmacologie Expérimentale et Clinique, Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Comportement et noyaux gris centraux [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Université européenne de Bretagne ( UEB ) -CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Troubles du comportement alimentaire de l'adolescent ( UMR_S 669 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Sud - Paris 11 ( UP11 ), Médecine légale, Anatomo-pathologie et Paléopathologie, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP Hôpital Raymond Poincaré [Garches], Laboratoire Ethique Politique et Santé ( EA 4569 ), Université Paris Descartes - Paris 5 ( UPD5 ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Laboratoire de Pharmacologie Expérimentale et Clinique, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse, Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Université de Rennes (UR)-Université de Rennes (UR)-Université de Rennes 1 - Faculté de Médecine (UR1 Médecine), and BMC, Ed.

Subjects
medicine.medical_specialty, Psychotherapist, Alternative medicine, Major depressive disorder, Placebo, Publication bias, 03 medical and health sciences, 0302 clinical medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, 030212 general & internal medicine, Psychiatry, Depression (differential diagnoses), Medicine(all), Fluoxetine, business.industry, Rank (computer programming), General Medicine, Antidepressants, medicine.disease, 3. Good health, Meta-analysis, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], business, 030217 neurology & neurosurgery, Research Article, medicine.drug
Abstract

International audience; BACKGROUND: Antidepressants are often considered to be mere placebos despite the fact that meta-analyses are able to rank them. It follows that it should also be possible to rank different placebos, which are all made of sucrose. To explore this issue, which is rather more epistemological than clinical, we designed an unusual meta-analysis to investigate whether the effects of placebo in one situation are different from the effects of placebo in another situation. METHODS: Published and unpublished studies were searched for by three reviewers on Medline, the Cochrane Library, Embase, clinicaltrials.gov, Current Controlled Trial, in bibliographies, and by mailing key organizations. The following studies in first-line treatment for major depressive disorder were considered to construct an "evidence network": 1) randomized controlled trials (RCTs) versus placebo on fluoxetine, venlafaxine and 2) fluoxetine versus venlafaxine head-to-head RCTs.Two network meta-analyses were run to indirectly compare response and remission rates among three different placebos: 1) fluoxetine placebo, 2) venlafaxine placebo, and 3) venlafaxine/fluoxetine placebo (that is, placebo compared to both venlafaxine and fluoxetine). Publication biases were assessed using funnel plots and statistically tested. RESULTS: The three placebos were not significantly different in terms of response or remission. The antidepressant agents were significantly more efficacious than the placebos, and venlafaxine was more efficacious than fluoxetine. The funnel plots, however, showed a major publication bias. CONCLUSION: The presence of significant levels of publication bias indicates that we cannot even be certain of the conclusion that sucrose equals sucrose in trials of major depressive disorder. This result should remind clinicians to step back to take a more objective view when interpreting a scientific result. It is of crucial importance for their practice, far more so than ranking antidepressant efficacy.

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